This proposal requests partial support for a new Gordon Research Conference on Metallocofactors as part of the Gordon Research Conference series to be held in Stonehill College (Easton, MA) on June 12-17, 2016 with a broad and long-term goal of bringing together the world's leading experts in metallocofactor biology and chemistry, focusing on enzymatic mechanisms, model complexes, biogenesis, and roles in regulation and human disease in a uniquely cross disciplinary manner. Metallocofactors play essential roles in biology. Understanding these roles and how to exploit them in the context of human health fits well within the NIGMS mission. In nutrition, the importance of essential trace elements reflects their functions as cofactors. In humans these include iron, magnesium, manganese, cobalt, copper, zinc, and molybdenum. Iron-sulfur (FeS) clusters for instance serve as prosthetic groups that confer unique chemical capabilities upon proteins. FeS proteins are also represented in the most central metabolic pathways, including the citric acid cycle and the mitochondrial respiratory chain, the latter of which depends on twelve FeS clusters for function. FeS enzymes play critical roles in the generation of radicals, as demonstrated by the very diverse family of SAM-dependent enzymes. Structurally interesting metallocofactors featuring Fe, Mn, Mo, Ni, and Cu are present in many bacteria and mediate remarkable metabolic redox chemistry with small molecule substrates including N2, H2O, H2, CO2, N2O, and CH4. Current interest in understanding how these metallocofactors function at the atomic level is enormous, especially in the context of sustainably feeding and fueling our planet; if we can understand how they work, there exists the possibility to design synthetic catalysts that function similarly with practical consequences in the realm of sustainability and human health. The aim of this conference is to include young and distinguished speakers and discussion leaders from different fields/skillsets related by the common theme of metallocofactors and biology. The health relevance of this meeting is strong, and mixing chemists, biochemists, structural biologists, molecular biologists, theorists, and medical researchers together in the context of the metallocofactor theme has the potential to catalyze much progress in the field.